Mechanobiology of Colorectal Cancer

SIMPLE SUMMARY: It is well documented that colorectal cancer (CRC) is the third most common cancer type, responsible for high mortality in developed countries, resulting in a high socio-economic impact. Several biochemical and gene expression pathways explaining the manifestation of this cancer in humans have already been identified. However, explanations for some of the related biophysical mechanisms and their influence on CRC remain elusive. In CRC, biophysics and medical research have already revealed the importance of studying the effects of the stiffness and viscoelasticity of the substrate on cells, as well as the effect of the shear stress of blood and lymphatic vessels on the behavior of cells and tissues. A deeper understanding of the relationship between the biophysical cues and biochemical signals could be advantageous to develop new diagnostic techniques and therapeutic strategies. Being a disease with a high mortality rate, it becomes crucial to dedicate efforts to finding effective, alternative therapeutic strategies. ABSTRACT: In this review, the mechanobiology of colorectal cancer (CRC) are discussed. Mechanotransduction of CRC is addressed considering the relationship of several biophysical cues and biochemical pathways. Mechanobiology is focused on considering how it may influence epithelial cells in terms of motility, morphometric changes, intravasation, circulation, extravasation, and metastization in CRC development. The roles of the tumor microenvironment, ECM, and stroma are also discussed, taking into account the influence of alterations and surface modifications on mechanical properties and their impact on epithelial cells and CRC progression. The role of cancer-associated fibroblasts and the impact of flow shear stress is addressed in terms of how it affects CRC metastization. Finally, some insights concerning how the knowledge of biophysical mechanisms may contribute to the development of new therapeutic strategies and targeting molecules and how mechanical changes of the microenvironment play a role in CRC disease are presented.